Bisphosphonates adverse events meta-analysis: comparing healthy and cancer patients
2020-02-28
Bisphosphonate effects on events compared between cancer and healthy patients.
Just two studies of bisphosphonates for preventing osteoperosis in “healthy” women without cancer: FIT and Horizon.
HORIZON: two papers reported on the same population, one reporting acute events following the start of treatment, and one with longer follow-up. It’s unclear whether some of the same events are repeated between the two reports.
FIT: two papers, one reporting the full trial population and the other reporting a subgroup. The only events reported were abdominal pain, oesophagitis, dyspepsia, gastrointestinal (unspecified) and nausea.
The table below compares the odds ratios from the network meta-analysis of bisphosphonates in women with cancer with the equivalent odds ratios from a simple meta-analysis of HORIZON and FIT, for the events that are significant in the cancer analysis and also reported in HORIZON and FIT.
## Warning: Column `event` joining factors with different levels, coercing to character vector
## Warning: Column `event` joining character vector and factor, coercing into character vectorTreatment (cancer NMA) | OR (Cancer, NMA) | Treatment (healthy MA) | OR (healthy MA) | ||
MYALGIA | |||||
MYALGIA | Ibandronate | 2.04 (1.13, 3.85) | Bisphosphonate | 5.99 (4.59, 7.81) | |
MYALGIA | Pamidronate | 2.32 (1.09, 5.21) | Bisphosphonate | 5.99 (4.59, 7.81) | |
MYALGIA | Zoledronic_acid | 2.36 (1.61, 3.6) | Bisphosphonate | 5.99 (4.59, 7.81) | |
OTHERS | |||||
ABDOMINAL PAIN | Bisphosphonate | 1.51 (1.1, 2.11) | Bisphosphonate | 1.11 (0.97, 1.27) | |
ARTHRALGIA | Nitrogenous | 1.54 (1.28, 1.86) | Bisphosphonate | 3.54 (2.74, 4.59) | |
CARDIAC EVENTS | Nitrogenous | 2.73 (1.33, 6.31) | Bisphosphonate | 1.29 (0.95, 1.76) | |
CARDIAC EVENTS | Non_nitrogenous | 4.35 (1.44, 13.6) | Bisphosphonate | 1.29 (0.95, 1.76) | |
CHILLS | Zoledronic_acid_IV | 15.19 (3.96, 94.86) | Bisphosphonate | 7.71 (4.98, 11.95) | |
DIARRHOEA | Non_nitrogenous | 1.81 (1.35, 2.74) | Bisphosphonate | 2.41 (1.48, 3.92) | |
FATIGUE | Bisphosphonate | 1.28 (1.06, 1.65) | Bisphosphonate | 3.37 (2.53, 4.49) | |
FEVER | Pamidronate_IV | 4.87 (1.9, 12.62) | Bisphosphonate | 10.11 (8.5, 12.01) | |
FEVER | Zoledronic_acid_IV | 5.2 (2.88, 8.79) | Bisphosphonate | 10.11 (8.5, 12.01) | |
HEADACHE | Zoledronic_acid | 1.48 (1.06, 2.25) | Bisphosphonate | 3.5 (2.9, 4.21) | |
Influenza-like symptoms | Bisphosphonate | 16.09 (2.04, 207.85) | Bisphosphonate | 5.86 (4.77, 7.19) | |
NAUSEA | Bisphosphonate | 1.33 (1.11, 1.63) | Bisphosphonate | 1.95 (1.57, 2.42) | |
THROMBOEMBOLIC EVENTS | Clodronate | 7.27 (1.41, 33.44) | Bisphosphonate | 0.99 (0.73, 1.33) | |
THROMBOEMBOLIC EVENTS | Ibandronate | 13.15 (2.36, 68.93) | Bisphosphonate | 0.99 (0.73, 1.33) | |
THROMBOEMBOLIC EVENTS | Zoledronic_acid | 2.79 (0.99, 7.42) | Bisphosphonate | 0.99 (0.73, 1.33) | |
VOMITING | Non_nitrogenous | 1.67 (1.18, 2.92) | Bisphosphonate | 12.35 (5.37, 28.42) |
Events deemed significant in a fixed effects meta analysis of HORIZON/FIT, using same criterion as in the main analysis: statistically significant OR > 1.5 or risk difference > 0.02.
Odds ratio | Risk difference | |
NAUSEA | 1.95 (1.57, 2.42) | 0.01 (0.01, 0.01) |
ARTHRALGIA | 3.54 (2.74, 4.59) | 0.02 (0.01, 0.02) |
FEVER | 10.11 (8.5, 12.01) | 0.1 (0.1, 0.11) |
HEADACHE | 3.5 (2.9, 4.21) | 0.03 (0.03, 0.04) |
Influenza-like symptoms | 5.86 (4.77, 7.19) | 0.05 (0.04, 0.05) |
MYALGIA | 5.99 (4.59, 7.81) | 0.03 (0.02, 0.03) |
CHILLS | 7.71 (4.98, 11.95) | 0.01 (0.01, 0.02) |
DEHYDRATION | 23.01 (1.36, 390.54) | 0 (0, 0) |
DIARRHOEA | 2.41 (1.48, 3.92) | 0 (0, 0) |
DIZZINESS | 1.89 (1.28, 2.78) | 0 (0, 0.01) |
FATIGUE | 3.37 (2.53, 4.49) | 0.01 (0.01, 0.02) |
HOT FLUSHES | 2.7 (1.31, 5.6) | 0 (0, 0) |
LOSS OF APPETITE | 6.48 (2.92, 14.38) | 0 (0, 0) |
MUSCULOSKELETAL PAIN/EVENT | 4.97 (4.19, 5.88) | 0.05 (0.05, 0.06) |
Nasopharyngitis | 3.4 (1.25, 9.23) | 0 (0, 0) |
OEDEMA | 4.5 (1.52, 13.32) | 0 (0, 0) |
OTHER EYE DISORDERS | 11.03 (2.59, 46.93) | 0 (0, 0) |
VOMITING | 12.35 (5.37, 28.42) | 0.01 (0, 0.01) |
The study-specific odds ratios underlying these results are shown below.
For each event, the odds ratios from HORIZON and FIT are not surprising given the variability between studies.
TODO CHANGE THIS TO ONE COL PER EVENT. THREE OR FOUR PLOTS
